Weak Forces

A FALLING FEATHER exerts negligible pressure on the surface it lands upon. In the macro world, such impact is of no consequence. In the diminutive world of the cell, though, many events depend on exquisitely subtle effects. But because the forces involved are so weak—as little as 0.5 piconewtons—it has been difficult to detect and study such events.

Now, a new technique allows researchers to measure changes on biological molecules caused by weak forces (Science 2007, 318, 279). With this tool, researchers could gain insights into processes or systems where weak forces play a regulatory function, such as DNA synthesis or ion channels proposed to be involved in hearing.

At the cellular level, weak forces are far more biologically relevant than strong forces, says Taekjip Ha, a biophysicist at the University of Illinois, Urbana-Champaign, and leader of the team that did the study. Most single-molecule mechanical techniques, he notes, work well only with strong persistent forces.

The new technique combines fluorescence spectroscopy with optical tweezers, in which a laser beam is used to trap and manipulate objects. The researchers use optical tweezers to apply a small force to a fluorescence-labeled object and detect the effect of the applied force on the object's shape by way of fluorescence signals.

Ha and coworkers used the technique to study the effects of small forces on the four-armed DNA structure known as a Holliday junction, which is involved in DNA recombination. They found significant changes in the structure even at forces as weak as 0.5 pN. The conformational changes caused by such forces can't be measured by traditional force experiments, which generally require forces of 10 pN or higher.